Platelet count and outcome in patients with acute venous thromboembolism.

The relationship between platelet count and outcome in patients with acute venous thromboembolism (VTE) has not been consistently explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We categorised patients as having very low- (<80,000/µl), low- (80,000/µl to 150,000/µl), normal- (150,000/µl to 300,000/µl), high- (300,000/µl to 450,000/µl), or very high (>450,000/µl) platelet count at baseline, and compared their three-month outcome. As of October 2012, 43,078 patients had been enrolled in RIETE: 21,319 presenting with pulmonary embolism and 21,759 with deep-vein thrombosis. In all, 502 patients (1.2%) had very low-; 5,472 (13%) low-; 28,386 (66%) normal-; 7,157 (17%) high-; and 1,561 (3.6%) very high platelet count. During the three-month study period, the recurrence rate was: 2.8%, 2.2%, 1.8%, 2.1% and 2.2%, respectively; the rate of major bleeding: 5.8%, 2.6%, 1.7%, 2.3% and 4.6%, respectively; the rate of fatal bleeding: 2.0%, 0.9%, 0.3%, 0.5% and 1.2%, respectively; and the mortality rate: 29%, 11%, 6.5%, 8.8% and 14%, respectively. On multivariate analysis, patients with very low-, low-, high- or very high platelet count had an increased risk for major bleeding (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.85-3.95; 1.43 [1.18-1.72]; 1.23 [1.03-1.47]; and 2.13 [1.65-2.75]) and fatal bleeding (OR: 3.70 [1.92-7.16], 2.10 [1.48-2.97], 1.29 [0.88-1.90] and 2.49 [1.49-4.15]) compared with those with normal count. In conclusion, we found a U-shaped relationship between platelet count and the three-month rate of major bleeding and fatal bleeding in patients with VTE.

Optic perineuritis secondary to Wegener's granulomatosis.

BACKGROUND: Optic perineuritis (OPN) is an inflammatory condition involving the optic nerve sheath because of a variety of causes. We describe three patients in whom OPN was secondary to Wegener's granulomatosis (WG) and compare the clinical findings in these cases with those of idiopathic OPN. METHODS: This is a retrospective small case series derived from patients with OPN seen in an outpatient neuro-ophthalmology clinic. Medical records and imaging studies of these patients were reviewed. RESULTS: These patients shared clinical similarities with idiopathic OPN including age, sex, symptoms, radiographic findings and steroid responsiveness. However, recurrence of symptoms on lowering the prednisone dose below 40 mg distinguished these patients from those with idiopathic OPN. CONCLUSIONS: Steroid dependency in idiopathic OPN should raise suspicion of WG. Patients with OPN should be specifically questioned regarding pre-existing upper respiratory tract disorders and rheumatic symptoms and laboratory testing should include acute phase reactants, anti-neutrophil cytoplasmic antibodies and tests of renal function.

Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis.

OBJECTIVE: Familial cold urticaria (FCU) and Muckle-Wells syndrome (MWS) are dominantly inherited autoinflammatory disorders that cause rashes, fever, arthralgia, and in some subjects, AA amyloidosis, and have been mapped to chromosome 1q44. Sensorineural deafness in MWS, and provocation of symptoms by cold in FCU, are distinctive features. This study was undertaken to characterize the genetic basis of FCU, MWS, and an overlapping disorder in French Canadian, British, and Indian families, respectively. METHODS: Mutations in the candidate gene NALP3, which has also been named CIAS1 and PYPAF1, were sought in the study families, in a British/Spanish patient with apparent sporadic MWS, and in matched population controls. Identified variants were sought in 50 European subjects with uncharacterized, apparently sporadic periodic fever syndromes, 48 subjects with rheumatoid arthritis (RA), and 19 subjects with juvenile idiopathic arthritis (JIA). RESULTS: Point mutations, encoding putative protein variants R262W and L307P, were present in all affected members of the Indian and French Canadian families, respectively, but not in controls. The R262W variant was also present in the subject with sporadic MWS. The V200M variant was present in all affected members of the British family with MWS, in 2 of the 50 subjects with uncharacterized periodic fevers, and in 1 of 130 Caucasian and 2 of 48 Indian healthy controls. No mutations were identified among the subjects with RA or JIA. CONCLUSION: These findings confirm that mutations in the NALP3/CIAS1/PYPAF1 gene are associated with FCU and MWS, and that disease severity and clinical features may differ substantially within and between families. Analysis of this gene will improve classification of patients with inherited or apparently sporadic periodic fever syndromes.

Human papillomavirus infection and cervical cancer in Brazil: a retrospective study

Two hundred and thirty paraffin-embedded biopsies obtained from female cervical lesions were tested for the presence of human papillomavirus (HPV) types 6/11,16/18 and 31/33/35 DNA using non-isotopic in situ hybridization. Specimens were classified according to the Bethesda System in low grade squamous intraepithelial lesion (LSIL), high grade SIL (HSIL) and squamous cell carcinoma (SCC). HPV prevalence ranged from 92.5% in LSIL to 68.5% in SCC. Benign types were prevalent in LSILs while oncogenic types infected predominantly HSILs and SCC. HPV infection showed to be age-dependent, but no significant relation to race has been detected. Patients were analyzed through a five-year period: 20.7% of the lesions spontaneously regressed while 48.9% persisted and 30.4% progressed to carcinoma. Patients submitted to treatment showed a 19.4% recurrence rate. High risk types were present in 78.6% (CrudeOR 13.8, P=0.0003) of the progressive lesions, and in 73.7% of the recurrent SILs (COR 19.3, P=0.0000001). Possible co-factors have also been evaluated: history of other sexually transmitted diseases showed to be positively related either to progression (Adjusted OR 13.0, P=0.0002) or to recurrence (AOR 17.2, P=0.0002) while oral contraceptive use and tobacco smoking were not significantly related to them (P>0.1). Association of two or more co-factors also proved to be related to both progression and recurrence, indicating that they may interact with HPV infection in order to increase the risk of developing malignant lesions.

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group.

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

Der Radioimmunoassay zur Ermittlung des carcinoembryonalen Antigens (CEA), seine Bedeutung und Limitierung während der postoperativen Kontrollperiode von Patienten mit colorectalem Carcino

Carcinoembryonic antigen (CEA) is a tumor marker defined by specific heterologous antisera. Elevated levels of circulating CEA can be detected by radioimmunoassay in most cases of colorectal carcinoma, depending on the degree of tumor spread. The fact that elevation of CEA level can also be observed in other types of carcinomas and in several nonmalignant conditions greatly limits the value of the CEA test for the early diagnosis of colorectal carcinomas. Repeated CEA measurements and their critical interpretation, however, appear to be of importance after tumor resection for the detection of tumor recurrence during the postoperative follow-up period.

The type of K-ras mutation determines prognosis in colorectal cancer.

BACKGROUND: Mutations involving the oncogene K-ras in colorectal cancer may be related to tumor aggressiveness. However, the value of K-ras gene determination as a prognostic marker has not been clearly established. PATIENTS AND METHODS: The results from 98 patients recruited in a prospective study analyzing the effect of a K-ras mutation as a prognostic factor in colorectal cancer are reported. RESULTS: Disease-free (P = 0.02) and overall survival (P = 0.03) were significantly reduced for patients harboring a K-ras mutation. Two specific mutations demonstrated a significantly increased risk of disease recurrence, namely, 12-TGT (P = 0.04) and 13-GAC substitutions (P = 0.002). Patients with either of these substitutions had a 2-year disease-free survival rate of 37% compared with that of 67% for the group of patients harboring any other mutation type or a wild-type status (P = 0.01). CONCLUSIONS: The results herein presented suggest that K-ras acts as a prognostic factor in colorectal cancer and that this effect is probably related to a limited number of defined mutations.

La définition des interfaces pour améliorer la qualité: l'exemple de l'anorexie en hospitalisation somatique [Defining interfaces to improve quality of care: the example of anorexia nervosa in acute somatic hospitalisation]

Specialisation in medicine requires multidisciplinary approaches, and hence coordination in collaborations of the different partners involved. These integrated approaches, sometimes called "disease management", fit particularly well to chronic diseases. Our institution introduced an integrated approach for taking care of the acute somatic hospitalisation of patients suffering from anorexia nervosa. Interfaces with the different partners were defined, specifying tasks, rights, and duties of each person, care givers or patients. This initiative allows now to identify any deviation occurring in the process of care or hole in the care system, so that it can be corrected and recurrence prevented. This model will be extended to other complex and multidisciplinary care processes and other services in our institution.

Appropriateness of colonoscopy in Europe (EPAGE II). Surveillance after polypectomy and after resection of colorectal cancer.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for surveillance after polypectomy and after curative-intent resection of colorectal cancer (CRC), and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of surveillance colonoscopy after polypectomy and after resection of CRC was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: Most CRCs arise from adenomatous polyps. The characteristics of removed polyps, especially the distinction between low-risk adenomas (1 or 2, small [< 1 cm], tubular, no high-grade dysplasia) vs. high-risk adenomas (large [> or = 1 cm], multiple [> 3], high-grade dysplasia or villous features), have an impact on advanced adenoma recurrence. Most guidelines recommend a 3-year follow-up colonoscopy for high-risk adenomas and a 5-year colonoscopy for low-risk adenomas. Despite the lack of evidence to support or refute any survival benefit for follow-up colonoscopy after curative-intent CRC resection, surveillance colonoscopy is recommended by most guidelines. The timing of the first surveillance colonoscopy differs. The expert panel considered that 56 % of the clinical indications for colonoscopy for surveillance after polypectomy were appropriate. For surveillance after CRC resection, it considered colonoscopy appropriate 1 year after resection. CONCLUSIONS: Colonoscopy is recommended as a first-choice procedure for surveillance after polypectomy by all published guidelines and by the EPAGE II criteria. Despite the limitations of the published studies, colonoscopy is also recommended by most of the guidelines and by EPAGE II criteria for surveillance after curative-intent CRC resection.

Acute hypersensitivity pneumonitis in a paint quality controller : a case report

Introduction: Isocyanates are sensitizing chemicals used in various industries such as polyurethane foam production or paint-related purposes. Acting as haptens recognized by T-lymphocytes, they can cause allergic asthma and rarely hypersensitivity pneumonitis (HP). We aim to present a case report of acute HP due to hexamethylene diisocyanate (HDI) in a paint quality controller, a profession not generally considered at a high risk for work-related Isocyanates exposure. Case report: A 30-yr-old otherwise healthy female, light smoker working as a paint quality controller developed shortness of breath, malaise, sweating and chills at workplace six hours after handling a HDI-based hardener. Upon admission to emergency department, symptoms had progressed to severe respiratory failure. HR computer tomography (HRCT) showed bilateral ground-glass attenuation without pleural effusion. Rapid clinical and radiological improvement occurred under facial oxygen supply and systemic steroid therapy. Occupational medicine investigations revealed regular handling of HDI using latex gloves without respiratory protection. Assessment at workplace showed insufficient air renewal (1.5 times per hour), inadequate local aspiration and HDI exposure at levels of 1-4.25 ppb/m3 (Swiss Occupation Exposure Limit 5 ppb/m3). Biological monitoring after identical work procedure executed by a co-worker showed HDI exposure (5.1 micrograms hexamethylene diamine/g creatinine). Resumption of work was disadvised because of the life-threatening event. Discussion: The diagnosis of occupational HP is highly supported by classical findings on imagery and typical symptoms occurring within approved latency interval, associated with rapid clinical improvement. Although neither broncho-alveolar lavage nor specific IgG diagnosis (en route) were performed during the acute episode, various blood tests managed to rule out evidence of an infection or autoimmune disease. Other causes of HP seem unlikely as the patient did not have any recurrence of symptoms since absence from work. Workplace evaluation provided significant information on HDI exposure and allowed substantial recommendations to diminish Isocyanate exposure for the 20 still healthy laboratory co-workers. Although the entryways (air or skin) and precise mechanism of toxicity remain unclear, the present case clearly shows that Isocyanates may trigger acute HP in susceptible workers in a profession not generally considered at a high risk.

Helical tomotherapy or intensity-modulated radiation therapy in the treatment of anal cancer: experience of Geneva and Lausanne

Background: To assess the early clinical outcomes and toxicities in patients treated with high precision radiation therapy (RT) consisting of helical tomotherapy (HT) or intensity-modulated radiation therapy (IMRT) for anal cancer. Materials and Methods: Since March 2006, 30 patients with stage I-IIIB anal squamous-cell carcinoma were treated curatively by IMRT or HT alone (n = 2) or by concomitant chemotherapy and IMRT or HT (n = 28). Median age was 59 years (range, 36−83 years) and the female/male ratio was 2.3 (21/9). Primary tumor site was anal canal, anal margin, or both in 26, 1, and 3 patients, respectively. Anal tumor, pelvic and inguinal nodes were irradiated with a median dose of 36 Gy using HT, or 5- or 7-field IMRT in 18 and 12 patients, respectively; After a planned gap of 1−2 weeks (median 1 week), a median boost dose of 23.4 Gwas delivered to the tumor and/or involved nodes using 3DRT (n = 24) or HT/IMRT (n = 6). The total delivered dose ranged between 59.4 and 64.8 Gy (median, 59.4 Gy). Concomitant chemotherapy consisted of mitomycin C alone (n = 1), mitomycin C and 5-fluorouracil (n = 17) or capecitabin (n = 10) in 28 patients. Common Terminology Criteria for Adverse Events v3.0 scale was used to score acute and late toxicities. Results: All but one patient, who developed progressive local and distant disease at the end of RT, achieved a complete response. Twelve months following RT, one patient had a recurrence at the primary tumor site, salvaged with brachytherapy. After a median follow-up of 7.5 months (range, 1−35 months), no deaths were observed. The 2-year actuarial locoregional control and probability of disease control without colostomy rates were 82% and 79%, respectively. RT was well tolerated without any unplanned treatment interruptions. Grade 1 or 2 acute adverse events consisted of skin toxicity in 8 and 22 patients, diarrhea in 18 and 3 patients, and cystitis in 9 and 2 patients; respectively. Only one patient developed grade 3 mucosal necrosis at the end of the treatment, requiring diverting colostomy. No difference in terms of acute toxicity was observed between patients treated with HT or IMRT. None of the 22 patients with a follow-up of more than 3 months developed grade 3 or more late toxicity. Conclusions: Our preliminary results suggest that HT or IMRT combined with concomitant chemotherapy for anal cancer is effective, and associated with favorable rates of toxicity compared with historical series. Further follow-up is warranted to assess late toxicity.

Repeat Gamma Knife surgery for recurrent trigeminal neuralgia: long-term outcomes and systematic review.

Object The purpose of this study was to establish the safety and efficacy of repeat Gamma Knife surgery (GKS) for recurrent trigeminal neuralgia (TN). Methods Using the prospective database of TN patients treated with GKS in Timone University Hospital (Marseille, France), data were analyzed for 737 patients undergoing GKS for TN Type 1 from July 1992 to November 2010. Among the 497 patients with initial pain cessation, 34.4% (157/456 with ≥ 1-year follow-up) experienced at least 1 recurrence. Thirteen patients (1.8%) were considered for a second GKS, proposed only if the patients had good and prolonged initial pain cessation after the first GKS, with no other treatment alternative at the moment of recurrence. As for the first GKS, a single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4-14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 90 Gy (range 70-90 Gy) was delivered. Data for 9 patients with at least 1-year followup were analyzed. A systematic review of literature was also performed, and results are compared with those of the Marseille study. Results The median time to retreatment in the Marseille study was 72 months (range 12-125 months) and in the literature it was 17 months (range 3-146 months). In the Marseille study, the median follow-up period was 33.9 months (range 12-96 months), and 8 of 9 patients (88.9%) had initial pain cessation with a median of 6.5 days (range 1-180 days). The actuarial rate for new hypesthesia was 33.3% at 6 months and 50% at 1 year, which remained stable for 7 years. The actuarial probabilities of maintaining pain relief without medication at 6 months and 1 year were 100% and 75%, respectively, and remained stable for 7 years. The systematic review analyzed 20 peer-reviewed studies reporting outcomes for repeat GKS for recurrent TN, with a total of 626 patients. Both the selection of the cases for retreatment and the way of reporting outcomes vary widely among studies, with a median rate for initial pain cessation of 88% (range 60%-100%) and for new hypesthesia of 33% (range 11%-80%). Conclusions Results from the Marseille study raise the question of surgical alternatives after failed GKS for TN. The rates of initial pain cessation and recurrence seem comparable to, or even better than, those of the first GKS, according to different studies, but toxicity is much higher, both in the Marseille study and in the published data. Neither the Marseille study data nor literature data answer the 3 cardinal questions regarding repeat radiosurgery in recurrent TN: which patients to retreat, which target is optimal, and which dose to use.